Screening, brief interventions, and referral to treatment (SBIRT) for drug use/abuse offers opportunities for early detection, brief intervention/treatment, and substance use treatment referrals for patients in medical settings. Although SBIRT components, particularly screening and brief interventions, have been shown to be effective strategies for addressing alcohol misuse in primary care, data are limited on using all of the components of SBIRT for drug-using patients, particularly in the Emergency Department (ED). Further, because of the often chaotic environment of EDs, many logistical and practical impediments exist for the adoption of the entire SBIRT model in this setting. Therefore, the proposed study will use computerized screening using touch screen computer tablets with audio (~4,900 patients) and will test intervention strategies in a two-factorial design (3x2). Specifically, 900 patients aged 18-60 in an inner-city ED who screen positive for drug use in the past 3 months will be randomized to the combinations of three ED-based conditions (computer brief intervention-CBI; intervener brief intervention-IBI ; enhanced usual care-EUC), and two follow-up conditions (adapted motivational enhancement therapy-AMET; enhanced usual care-EUC) that will take place 2 months post-ED. All individuals who meet criteria for a drug use disorder will additionally receive the referral to treatment or RT component of SBIRT. Stratified random assignment [by gender and diagnosis of a drug use disorder (yes/no)] will take place at baseline for all ED- based and follow-up conditions. All participants will receive written information including substance abuse and other community resources, and HIV prevention materials. Recognizing that brief interventions are important, but not necessarily sufficient, for change in all patients who use drugs, the primary specific aims of the proposed study will determine the independent effectiveness of immediate on-the-spot ED-based brief intervention conditions, 2-month follow- up brief treatment conditions, and combinations of conditions, for decreasing drug use and improving health-related outcomes (including physical and mental health, and HIV risk behavior) at 6 and 12 months. The use of state-of-the-art computer technology for screening and brief interventions has the potential to reach greater numbers of ED patients than is possible with in- person screening and brief intervention. Developing methods to efficiently and effectively optimize SBIRT components has wide-ranging and powerful public health implications for improving outcomes for patients who use drugs.